Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs

Tao,Hao; Lin,Yazhou; Zhang,Guoqing; Gu,Rui; Chen,Bohua

doi:10.3892/br.2016.731

Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs

Authors:
- Hao Tao
- Yazhou Lin
- Guoqing Zhang
- Rui Gu
- Bohua Chen
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Affiliations: Department of Orthopedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Spinal and Neural Function Reconstruction, China Rehabilitation Research Center, Beijing 100068, P.R. China
Published online on: August 1, 2016 https://doi.org/10.3892/br.2016.731
Pages: 357-360

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Abstract

Allogeneic bone marrow mesenchymal stem cell (BMSC) transplantation has been investigated worldwide. However, few reports have addressed the survival status of human BMSCs in the intervertebral discs (IVDs) in vivo following transplantation. The current study aimed to observe the survival status of human BMSCs in rabbit IVDs. The IVDs of 15 New Zealand white rabbits were divided into three groups: Punctured blank control group (L1‑2); punctured physiological saline control group (L2‑3); and punctured human BMSCs transfected with green fluorescent protein (GFP) group (L3‑4, L4‑5 and L5‑6). One, 2, 4, 6 and 8 weeks after transplantation the IVDs were removed and a fluorescence microscope was used to observe the density of GFP‑positive human BMSCs. The results indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post‑transplantation, no GFP‑positive cells were observed in the control groups, whereas GFP‑positive cells were apparent in the nucleus pulposus at all periods in the GFP‑labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post‑transplantation (P<0.001). Thus, it was identified that human BMSCs were able to survive in the rabbit IVDs for 8 weeks.

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1	Hoy D, Brooks P, Blyth F and Buchbinder R: The Epidemiology of low back pain. Best Pract Res Clin Rheumatol. 24:769–781. 2010. View Article : Google Scholar : PubMed/NCBI
2	Takahashi K, Aoki Y and Ohtori S: Resolving discogenic pain. Eur Spine J. 17(Suppl 4): 428–431. 2008. View Article : Google Scholar : PubMed/NCBI
3	Hillman M, Wright A, Rajaratnam G, Tennant A and Chamberlain MA: Prevalence of low back pain in the community: Implications for service provision in Bradford, UK. J Epidemiol Community Health. 50:347–352. 1996. View Article : Google Scholar : PubMed/NCBI
4	McMeeken J, Tully E, Stillman B, Nattrass C, Bygott IL and Story I: The experience of back pain in young Australians. Man Ther. 6:213–220. 2001. View Article : Google Scholar : PubMed/NCBI
5	Pye SR, Reid DM, Smith R, Adams JE, Nelson K, Silman AJ and O'Neill TW: Radiographic features of lumbar disc degeneration and self-reported back pain. J Rheumatol. 31:753–758. 2004.PubMed/NCBI
6	Hoyland JA, Le Maitre C and Freemont AJ: Investigation of the role of IL-1 and TNF in matrix degradation in the intervertebral disc. Rheumatology (Oxford). 47:809–814. 2008. View Article : Google Scholar : PubMed/NCBI
7	LeMaitre CL, Freemont AJ and Hoyland JA: Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol. 204:47–54. 2004. View Article : Google Scholar : PubMed/NCBI
8	LeMaitre CL, Freemont AJ and Hoyland JA: Accelerated cellular senescence in degenerate intervertebral discs: A possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther. 9:R452007. View Article : Google Scholar : PubMed/NCBI
9	Richardson SM, Knowles R, Tyler J, Mobasheri A and Hoyland JA: Expression of glucose transporters GLUT-1, GLUT-3, GLUT-9 and HIF-1alpha in normal and degenerate human intervertebral disc. Histochem Cell Biol. 129:503–511. 2008. View Article : Google Scholar : PubMed/NCBI
10	Zhao CQ, Wang LM, Jiang LS and Dai LY: The cell biology of intervertebral disc aging and degeneration. Ageing Res Rev. 6:247–261. 2007. View Article : Google Scholar : PubMed/NCBI
11	Kim KW, Chung HN, Ha KY, Lee JS and Kim YY: Senescence mechanisms of nucleus pulposus chondrocytes in human intervertebral discs. Spine J. 9:658–666. 2009. View Article : Google Scholar : PubMed/NCBI
12	Richardson SM, Walker RV, Parker S, Rhodes NP, Hunt JA, Freemont AJ and Hoyland JA: Intervertebral disc cell-mediated mesenchymal stem cell differentiation. Stem Cells. 24:707–716. 2006. View Article : Google Scholar : PubMed/NCBI
13	Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG and Kang JD: Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J. 8:888–896. 2008. View Article : Google Scholar : PubMed/NCBI
14	Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K and Hotta T: Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: Potential and limitations for stem cell therapy in disc regeneration. Spine. 30:2379–2387. 2005. View Article : Google Scholar : PubMed/NCBI
15	Wang YH, Yang B, Li WL and Li JM: Effect of the mixture of bone marrow mesenchymal stromal cells and annulus fibrosus cells in repairing the degenerative discs of rabbits. Genet Mol Res. 14:2365–2373. 2015. View Article : Google Scholar : PubMed/NCBI
16	Yi Z, Guanjun T, Lin C and Zifeng P: Effects of transplantation of htimp1-expressing bone marrow mesenchymal stem cells on the extracellular matrix of degenerative intervertebral discs in an in vivo rabbit model. Spine. 39:E669–E675. 2014. View Article : Google Scholar
17	Wang Y, Wu X, Wang F, Hong X, Bao J and Zhu L: An in vitro study on biological characteristics of bone marrow mesenchymal stem cells in microenvironment of premature senescence of nucleus pulposus cells. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 28:758–762. 2014.(In Chinese). PubMed/NCBI
18	Subhan RA, Puvanan K, Murali MR, Raghavendran HR, Shani S, Abdullah BJ, Abbas AA, Mohamed JA and Kamarul T: Fluoroscopy assisted minimally invasive transplantation of allogenic mesenchymal stromal cells embedded in HyStem reduces the progression of nucleus pulposus degeneration in the damaged ntervertebral disc: A preliminary study in rabbits. Scientific World Journal. 2014:8185022014. View Article : Google Scholar : PubMed/NCBI
19	Dagenais S, Caro J and Haldeman S: A systematic review of low back pain cost of illness studies in the United States and internationally. Spine J. 8:8–20. 2008. View Article : Google Scholar : PubMed/NCBI
20	Grunhagen T, ShiraziAdl A, Fairbank JC and Urban JP: Intervertebral disk nutrition: A review of factors influencing concentrations of nutrients and metabolites. Orthop Clin North Am. 42465–477. (vii)2011. View Article : Google Scholar : PubMed/NCBI
21	Ogata K and Whiteside LA: 1980 Volvo award winner in basic science. Nutritional pathways of the intervertebral disc. An experimental study using hydrogen washout technique. Spine. 6:211–216. 1981. View Article : Google Scholar : PubMed/NCBI
22	Soukane DM, ShiraziAdl A and Urban JP: Computation of coupled diffusion of oxygen, glucose and lactic acid in an intervertebral disc. J Biomech. 40:2645–2654. 2007. View Article : Google Scholar : PubMed/NCBI
23	Richardson SM, Mobasheri A, Freemont AJ and Hoyland JA: Intervertebral disc biology, degeneration and novel tissue engineering and regenerative medicine therapies. Histol Histopathol. 22:1033–1041. 2007.PubMed/NCBI
24	Levin DA, Hale JJ and Bendo JA: Adjacent segment degeneration following spinal fusion for degenerative disc disease. Bull NYU Hosp Jt Dis. 65:29–36. 2007.PubMed/NCBI
25	Sive JI, Baird P, Jeziorsk M, Watkins A, Hoyland JA and Freemont AJ: Expression of chondrocyte markers by cells of normal and degenerate intervertebral discs. Mol Pathol. 55:91–97. 2002. View Article : Google Scholar : PubMed/NCBI
26	Steck E, Bertram H, Abel R, Chen B, Winter A and Richter W: Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells. 23:403–411. 2005. View Article : Google Scholar : PubMed/NCBI
27	Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K, Tamura F and Sakai D: Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res. 26:589–600. 2008. View Article : Google Scholar : PubMed/NCBI
28	Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M, Nakai T, Ando K and Hotta T: Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials. 27:335–345. 2006. View Article : Google Scholar : PubMed/NCBI
29	Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, Nakai T, Ando K and Hotta T: Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: A potential therapeutic model for disc degeneration. Biomaterials. 24:3531–3541. 2003. View Article : Google Scholar : PubMed/NCBI
30	Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, et al: Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 30:42–48. 2002. View Article : Google Scholar : PubMed/NCBI
31	Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, et al: Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med. 5:309–313. 1999. View Article : Google Scholar : PubMed/NCBI
32	LeBlanc K, Tammik C, Rosendahl K, Zetterberg E and Ringdén O: HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 31:890–896. 2003. View Article : Google Scholar : PubMed/NCBI